Evaluation of ketoconazole tablet prepared using dry granulation technique with filler-binder excipients and disintegration agent

Ketoconazole is one of high-dose treatment drugs with flowability issue so that it is commonly formulated using wet granulation technique. However, the technique impacts stability of ketoconazole which it changes in color upon solvent usage. This research was conducted to study tablet quality of ketoconazole as function of certain excipients in dry granulation technique. Combination of spray dried lactose (SDL) and Avicel® PH-102 as filler-binder excipients and sodium starch glycolate (SSG) as a disintegration agent were used for the purpose. Ketoconazole tablets were formulated based on 2² factorial design. Evaluation was performed on tablet properties, then statistically analyzed using Minitab® software. Tablet hardness and disintegration time increased in increasing level of filler combination and SSG concentration, but a decrease was observed for friability and % dissolved ketoconazole. Both filler combination and disintegration agent exhibited insignificant effect toward tablet properties evaluated. According to overlay contour plot, it is predicted that the optimum formulation of ketoconazole tablet can be set into SDL-Avicel® PH-102 ratio of at least 3:1 or higher and SSG concentration is higher than 3.5%.